在依赖的酸盐输送基因SLC34A3中的罕见变异解释了尿路结石疾病遗传能力的缺失
Omid Sadeghi-Alavijeh1, Melanie M Y Chan1, Shabbir H Moochhala1
1Department of Renal Medicine, University College London, London, UK.
Kidney international
|July 6, 2023
概括
在SLC34A3基因的罕见变异显著增加尿路结石疾病的风险. 这一发现有助于解释这种疾病的遗传性,超出了常见变异.
科学领域:
- 遗传学 遗传学 是一个
- 腎臟病學 (nephrology) 是一種醫學專業.
- 泌尿器科 泌尿器科 泌尿器科 泌尿器科
背景情况:
- 尿路结石病 (USD) 影响了超过10%的英国人口,生活方式和遗传因素都有所贡献.
- 全基因组关联研究 (GWAS) 确定了常见的遗传变异,解释了5%的USD遗传性,留下了大量无法解释的部分.
- 研究了罕见的遗传变异,以了解美元的剩余遗传性.
研究的目的:
- 调查罕见的遗传变异对尿路结石疾病 (USD) 无法解释的遗传性的贡献.
- 为了确定与患上USD的风险增加相关的特定基因和变异.
主要方法:
- 全基因组测序和罕见变异测试对来自英国10万个基因组项目的374个无关的USD病例进行.
- 对24930个祖先匹配的对照进行了多基因风险评分.
- 对整个外体的关联分析发现了特定基因中罕见变异的显著丰富.
主要成果:
- 与对照组 (1.6%) 相比,SLC34A3基因中的单类罕见,预测有害变异在USD病例 (5%) 中显著丰富.
- 这种丰富在一个独立的数据集中得到复制,证实SLC34A3是危险因素.
- 在SLC34A3的变种对美元风险的影响比GWAS的多基因风险得分更大,从5.1%增加遗传性到14.2%.
结论:
- 罕见的SLC34A3基因变异是尿路结石疾病的重要遗传风险因素.
- 这些发现解释了美元的部分遗传性,而不是常见变体.
- SLC34A3变体的效果大小介于高度透的孟德尔变体和常见的GWAS变体之间.
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